The extracellular adherence protein from Staphylococcus aureus inhibits the classical and lectin pathways of complement by blocking formation of the C3 proconvertase (INM8P.361)

Autor: Jordan Woehl, Daphne Stapels, Brandon Garcia, Kasra Ramyar, Andrew Keightley, Maartje Ruyken, Georgia Sfyroera, Alexander Weber, Michal Zolkiewski, Daniel Ricklin, John Lambris, Suzan Rooijakkers, Brian Geisbrecht
Rok vydání: 2015
Předmět:
Zdroj: The Journal of Immunology. 194:195.5-195.5
ISSN: 1550-6606
0022-1767
Popis: The pathogenic bacterium Staphylococcus aureus actively evades many aspects of human innate immunity by expressing a series of small inhibitory proteins. A number of these proteins inhibit the complement system, with the majority of S. aureus acting on the alternative pathway, blocking the amplification loop. Only a few proteins act on the initial recognition cascades that constitute the classical pathway (CP) and lectin pathway (LP). By screening a collection of recombinant, secreted staphylococcal proteins, we identified the extracellular adherence protein (Eap) as a potent, specific inhibitor of both the CP and LP. We found that Eap blocked CP/LP-dependent activation of C3, but not C4, and that Eap likewise inhibited deposition of C3b on the surface of S. aureus cells. In turn, this significantly diminished the extent of S. aureus opsonophagocytosis and killing by neutrophils. This combination of functional properties suggested that Eap acts specifically at the level of the CP/LP C3 convertase (C4b2a). Indeed, we demonstrated a direct, nanomolar-affinity interaction of Eap with C4b. Eap binding to C4b inhibited binding of both full-length C2 and its C2b fragment, which indicated that Eap disrupts formation of the CP/LP C3 proconvertase (C4b2). As a whole, our results demonstrate that S. aureus inhibits two initiation routes of complement by expression of the Eap protein, and thereby define a novel mechanism of immune evasion.
Databáze: OpenAIRE
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